The aims of the total program are to investigate the rheological behavior of human red blood cells and white blood cells, to study the interactions of their membranes with the environment, to correlate membrane functions with molecular organization, and to evaluate the role of blood cell properties in circulatory regulation in health and disease. The rheology of normal and abnormal red blood cells and white blood cells is studied by biochemical techniques, measurements of mobility of fluorescent probes, and theoretical computation. Rheological data are correlated with the molecular organization of the membrane, especially membrane proteins and lipids and their interactions. A multidisciplinary approach is used to study: changes in membrane rheology following experimental manipulation of membrane composition and in disease states; the expression of antigens on cell exoface; properties of hexose receptor transport protein; energy balance in the aggregation of red blood cells and lymphocytes by macromolecular ligands; and the micromechanics of cell interactions, including cell killing by cytotoxic T-lymphocytes and blood cell adhesion to endothelium. The role of blood cell properties in affecting flow dynamics and metabolic transport is studied in the macro- and microcirculation, including investigations on the microcirculation of the human nail folds. The above projects are supported by core facilities in the Ultrastructure Laboratory, Hematology Clinic, Instrumentation Laboratory Computer Unit and Cell Culture Laboratory. The coordinated effort is aimed at elucidating the biochemical basis and physiological oles of the biophysical behavior of blood cells, with the ultimate goal of providing the fundamental knowledge needed to improve diagnosis and treatment of cardiovascular and blood diseases.